Pluromed, Inc. NIH SBIR Phase I Grant Application Internal Polymeric Vessel Occluder for Temporary Vascular Occlusion of the Kidney During Partial Nephrectomy Project Summary/Abstract Nephron-sparing surgery has become more common for the treatment of renal masses. With increasing experience, the need to control intraoperative renal bleeding is increasingly significant. This need is amplified by the trend in urologic surgery towards robotic and minimally invasive techniques where visibility can be severely limited by even small volumes of blood. As a result, many techniques have been developed to achieve hemostasis, including conventional suture repair, tissue sealants, radiofrequency ablation, laser ablation, water dissection, and microwave tissue coagulation. Pluromed has developed a biocompatible gel in which the blood vessel is filled with and occluded by the gel. The gel's working principle is based on the reverse thermosensitive properties of the polymer. At low temperatures, the polymeric solution is a liquid. As the temperature increases to body temperature, the viscosity of the solution rapidly increases several orders of magnitude to the consistency of a hard gel. Cooling the occlusion site, for example by applying ice, lowers the viscosity back to that of a liquid, dissolving the gel in blood and reestablishing blood flow. The gel has been developed for applications in anastomosis such as Off-Pump Bypass surgery (OPCAB), hemodialysis access, and tibial anastomosis. It has been shown to work very gently, neither compromising nor changing the biochemical make-up the arterial wall, as evidenced by measurements of the microvascular reactivity after filling and opening up the blood vessel. The proposal of this Phase I application is to apply the same principle to nephron-sparing surgery. In this approach, the renal artery leading to the diseased kidney is infused with the reverse thermosensitive gel. This has been shown to lead to cessation of blood flow within the renal parenchyma. It appears that, with the appropriate injection rate, the polymer flows downstream to occlude small, intra-renal vessels on both the arterial and venous sides of the circulation. This produces a completely bloodless surgical field, allowing speedy resection. After about 20 minutes the flow gradually resumes, with no apparent adverse consequences to the kidney. Return of blood flow may then be accelerated, if necessary, by cooling the kidney. Initial short-term in-vivo experiments indicate the feasibility of this approach. However, the polymer used in these preliminary experiments has a lower than optimal transition temperature for a solid organ. In a solid organ, such as the kidney, temperatures during the surgery may be higher than in exposed arteries where the company has greater experimental experience. A polymer solution with a higher transition temperature may be superior to the present formulation for solid organ applications. Furthermore, a more extensive animal study is needed to ascertain the relationship between rate/volume of injection and the expected downstream ischemic time. It is also necessary to develop an injection system that does not unduly increase the procedural time by requiring a long dissection of the artery or by requiring additional surgery to repair the artery at the injection site. Delineation of these parameters will allow for chronic animal experiments in Phase II and a clear path forward to subsequent clinical application with the declared involvement of Dr. John A. Libertino, Chairman of the Department of Urology at Lahey Clinic Medical Center. Pluromed, Inc. NIH SBIR Phase I Grant Application Internal Polymeric Vessel Occluder for Temporary Vascular Occlusion of the Kidney During Partial Nephrectomy [unreadable] [unreadable] [unreadable]